Interactions between leukotrienes and other inflammatory mediators/modulators in the microvasculature.

Abstract

Throughout its many years as a powerful smooth muscle stimulant of unknown chemical structure, slow-reacting substance of anaphylaxis (SRS-A) remained an intriguing entity, possibly implicated as a mediator of hypersensitivity reactions, in particular those concerned with allergic asthma. Elucidation of the chemical structure of SRS-A, and the realization that it was not a single substance but rather a mixture of interrelated leukotrienes (LTs), necessitated reappraisal of earlier data about the effects of SRS-A in pulmonary tissue. Furthermore, as the LT family grew larger, interest turned also to other tissues and organ systems, with the ultimate goal to disclose specific targets for the various LTs. It is now generally accepted that the LTs collectively provoke contraction of vascular and nonvascular smooth muscle, enhanced vascular permeability, and accumulation and activation of leukocytes. The LTs often operate with a potency that far exceeds that of traditional autacoids, and they have obvious key targets of action within the pulmonary and cardiovascular systems. It has been conclusively documented that LTs are important mediators in bronchial asthma, and data are accumulating that they are involved in a number of other disease states, such as rheumatoid arthritis, inflammatory bowel disease, glomerulonephritis, and cardiac disorders. This article summarizes the microvascular actions of LTs formed via the 5-lipoxygenase pathway, and the interplay of these LTs and some other eicosanoids and histamine in the process of inflammation.